CAI Guanjun,CUI Xinyuan,LI Wenyi,et al.Influence of Transcription Factor KLF16 on Lipid Metabolism in Non-alcoholic Fatty Liver Disease[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(04):582-592.
CAI Guanjun,CUI Xinyuan,LI Wenyi,et al.Influence of Transcription Factor KLF16 on Lipid Metabolism in Non-alcoholic Fatty Liver Disease[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(04):582-592. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2024.0410.
Influence of Transcription Factor KLF16 on Lipid Metabolism in Non-alcoholic Fatty Liver Disease
To explore the expression of transcription factor KLF16 in nonalcoholic fatty liver disease (NAFLD) and its effect on lipid metabolism.
Methods
2
An animal model of NAFLD was constructed in mice induced by a high-fat diet. The mice were divided into normal diet group (ND) and high fat diet group (HFD). NAFLD cell model was constructed by primary mouse liver cells induced by oleic acid. The cells were divided into control group (Control group) and oleic acid induction group (OA group). Real-time fluorescence quantitative PCR (RT-qPCR) and Western blot were used to detect KLF16 expression in NAFLD animal and cell models. In vitro and in vivo models of KLF16 knockdown were constructed by injection of adeno-associated virus (AAV) into mouse tail veins and transient transfection of cell siRNA. Hematoxylin-eosin staining (HE) and other methods were used to detect changes in lipid deposition in NAFLD models before and after KLF16 knockout. RT-qPCR was used to detect the expression of key genes of lipid metabolism in both cellular and animal NAFLD models before and after KLF16 knockdown. Western blot assay was used to detect the expression of endoplasmic reticulum stress protein in NAFLD model before and after KLF16 knockdown.
Results
2
The expression level of KLF16 was up-regulated in HFD group and OA group, and lipid deposition was increased in OA group after KLF16 was depressed. There was no change in TC level in hepatocytes between groups (
P
>
0.05), and TG level was increased in different degrees (
P
<
0.05,
P
<
0.001). At the same time, the change of KLF16 expression also caused the change of ER stress
protein expression in OA group.
Conclusion
2
The transcription factor KLF16 may alleviate lipid deposition in nonalcoholic fatty liver disease by endoplasmic reticulum stress.
Greenberg AS, Coleman RA, Kraemer FB, et al. The role of lipid droplets in metabolic disease in rodents and human[J]. J Clin Invest, 2011, 121(6): 2102-2110.
Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease[J]. Cell, 2021, 184(10): 2537-2564.
Li JZ,Li MR.Characteristics and treatment strategies for hepatocellular carcinoma caused by nonalcoholic fatty liver disease[J]. Chin J Hepatol,2022,30(12):1392-1396.
Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease - Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64(1): 73-84.
Ashraf NU, Sheikh TA. Endoplasmic reticulum stress and oxidative stress in the pathogenesis of non-alcoholic fatty liver disease[J]. Free Radic Res, 2015, 49(12): 1405-1418.
Baiceanu A, Mesdom P, Lagouge M, et al. Endoplasmic reticulum proteostasis in hepatic steatosis[J]. Nat Rev Endocrinol, 2016, 12(12): 710-722.
McConnell BB, Yang VW. Mammalian Krüppel-like factors in health and diseases[J]. Physiol Rev, 2010, 90(4): 1337-1381.
Sun N, Shen C, Zhang L, et al. Hepatic Krüppel-like factor 16 (KLF16) targets PPARα to improve steatohepatitis and insulin resistance[J]. Gut, 2021, 70(11): 2183-2195.
Diraison F, Moulin P, Beylot M. Contribution of hepatic de novo lipogenesis and reesterification of plasma non esterified fatty acids to plasma triglyceride synthesis during non-alcoholic fatty liver disease[J]. Diabetes Metab, 2003, 29(5): 478-485.
Wier BVD, Koek GH, Bast A, et al. The potential of flavonoids in the treatment of non-alcoholic fatty liver disease[J]. Crit Rev Food Sci Nutr, 2017, 57(4): 834-855.
Flessa CM, Kyrou L, Nasiri-Ansari N, et al. Endoplasmic reticulum stress and autophagy in the pathogenesis of non-alcoholic fatty liver disease (NAFLD): Current evidence and perspectives[J]. Curr Obes Rep, 2021, 10(2): 134-161.
Fujii J, Homma T, Kobayashi S, et al. Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease[J]. World J Biol Chem, 2018, 9(1): 1-15.
Gariani K, Menzies KJ, Ryu D, et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice[J]. Hepatology, 2016, 63(4): 1190-1204.
Chen Z, Tian R, She Z, et al. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease[J]. Free Radic Biol Med, 2020, 152: 116-141.
Zhang B, Li M, Zou Y, et al. Corrigendum: NFκB/Orai1 facilitates endoplasmic reticulum stress by oxidative stress in the pathogenesis of non-alcoholic fatty liver disease[J]. Front Cell Dev Biol, 2019, 7: 290.
Nassir F. NAFLD: mechanisms, treatments, and biomarkers[J]. Biomolecules, 2022, 12(6):824.
Geng Y, Faber KN, Meijer VE, et al. How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease[J]. Hepatol Int, 2021, 15(1): 21-35.
Liu NC,Duan ZP,Zheng SP. Nonalcoholic fatty liver disease and bilirubin: correlation, mechanism, and therapeutic perspectives[J]. Chin J Hepatol,2023,31(1):101-104.
Xu R, Pan J, Zhou W, et al. Recent advances in lean NAFLD[J]. Biomed Pharmacother, 2022, 153: 113331.
Yuce K, Ozkan AI. The kruppel-like factor (KLF) family, diseases, and physiological events[J]. Gene, 2024, 895: 148027.
Ma XD, Xu SD, Hao SH, et al. KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming[J]. Mol Ther, 2022, 30(8): 2828-2843.
Zhang JX, Yan XJ, Wu S, et al. KLF16 overexpression deleteriously affects the proliferation and migration of retinoblastoma by transcriptionally repressing BCL2L15[J]. Biochem Biophys Res Commun, 2020, 529(4): 977-983.
Kim JK, Lee KS, Chang HY, et al. Progression of diet induced nonalcoholic steatohepatitis is accompanied by increased expression of Kruppel-like-factor 10 in mice[J]. J Transl Med, 2014, 12: 186.
Ajoolabady A, Kaplowitz N, Lebeaupin C, et al. Endoplasmic reticulum stress in liver diseases[J]. Hepatology, 2023, 77(2): 619-639.
Mi XX,Yan J,Shi JP.Improvement situation on indexes of the zebrafish disease model of non-alcoholic fatty liver disease with FGF21 analogues[J].Chin J Hepatol,2023,31(7):742-749.
Svegliati-Baroni G, Pierantonelli I, Torquato P, et al. Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease[J]. Free Radic Biol Med, 2019, 144: 293-309.
Clinical Significance of High Expression of Endoplasmic Reticulum Stress-related Proteins Glucose-regulating Protein 78 and X-box Binding Protein 1 induced by Fusobacterium Nucleatum in Esophageal Squamous Cell Carcinoma
Effects of Endoplasmic Reticulum Stress in Inducing Inflammation in Vascular Endothelial Cell
Endoplasmic Reticulum Stress and Kidney Diseases
Involvement Endoplasmic Reticulum Stress on Process of Nonalcoholic Fatty Liver Disease
Induced by MCD
Related Author
CHEN Si-mo
ZHANG Zhe-yuan
ZHANG Jia-hao
HE Ke-yao
LIU Yi-wen
ZHOU Fu-you
王蔚东
方婉军
Related Institution
Department of Thoracic Surgery, The Third Affiliated Hospital of Xinxiang Medical University
College of Clinical Medicine of Henan University of Science and Technology // The First Affiliated Hospital of Henan University of Science and Technology // Henan Key Laboratory of Cancer Epigenetics // Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment
Department of Thoracic Surgery, Anyang Tumor Hospital // Henan Key Laboratory of Precision Medicine for Prevention and Treatment of Esophageal Cancer
Institute of Hypertension,Zhongshan School of Medicine,2. Cardiovascular Research Program,Zhongshan school of Medicine,Sun Yat-sen Universtiy
Guangzhou Provincial Key Laboratory of Food,Nutrition and Health//Department of Nutrition,School of Public Health,Sun Yat-sen University